Meta-analysis of Increased Heart Rate and Blood Pressure Associated with CNS Stimulant Treatment of ADHD in Adults

Compared to children, adults with ADHD are at greater risk for developing adverse cardiovascular related outcomes and, if treated, may be likely to carry a greater burden of exposure to stimulant medications. The goal of this report is to critically review the available literature relevant to the cardiovascular safety of CNS stimulants for adult ADHD (aADHD). Twenty potential clinical trials of a CNS stimulant for aADHD have been published between 1979 and 2012. Of these, ten presented sufficient data to estimate the relative change in various cardiovascular parameters associated with ADHD treatment modalities. These trials were predominantly focused on long-acting stimulant preparations for acute symptom reduction (median duration=6 weeks, range: 4-24 weeks) and enrolled relatively young subjects (median age=36 years, range: 22-40). Using random effects meta-analysis, we found that subjects randomized to CNS stimulant treatment demonstrated a statistically significant increased resting heart rate [+5.7bpm (3.6, 7.8), p<0.001] and systolic blood pressure findings [+2.0mmHg (0.8, 3.2), p=0.005] compared with subjects randomized to placebo. There was a statistically significant increased risk for a resting heart rate >90bpm [4.2% (n=50) vs. 1.7% (n=8), OR=2.75 (1.3, 6.7), p=0.006] associated with CNS stimulant treatment. In light of prognostic value of resting heart rate with regard to cardiovascular morbidity in epidemiological studies, future research of adults with ADHD should focus on the potential clinical impact of the increase in heart rate observed in this meta-analysis.